Studies have shown that tumor microenvironment (TME) might affect drug sensitivity and the classification of colorectal cancer (CRC). Using TME-specific gene signature to identify CRC subtypes with distinctive clinical relevance has not yet been tested. A total of 18 "bulk" RNA-seq datasets (total n?=?2269) and four single-cell RNA-seq datasets were included in this study. We constructed a "Signature associated with FOLFIRI resistant and Microenvironment" (SFM) that could discriminate both TME and drug sensitivity. Further, SFM subtypes were identified using K-means clustering and verified in three independent cohorts. Nearest template prediction algorithm was used to predict drug response. TME estimation was performed by CIBERSORT and microenvironment cell populations-counter (MCP-counter) methods. We identified six SFM subtypes based on SFM signature that discriminated both TME and drug sensitivity. The SFM subtypes were associated with distinct clinicopathological, molecular and phenotypic characteristics, specific enrichments of gene signatures, signaling pathways, prognosis, gut microbiome patterns, and tumor lymphocytes infiltration. Among them, SFM-C and -F were immune suppressive. SFM-F had higher stromal fraction with epithelial-to-mesenchymal transition phenotype, while SFM-C was characterized as microsatellite instability phenotype which was responsive to immunotherapy. SFM-D, -E, and -F were sensitive to FOLFIRI and FOLFOX, while SFM-A, -B, and -C were responsive to EGFR inhibitors. Finally, SFM subtypes had strong prognostic value in which SFM-E and -F had worse survival than other subtypes. SFM subtypes enable the stratification of CRC with potential chemotherapy response thereby providing more precise therapeutic options for these patients.Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n?=?35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n?=?150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18-2.87, p?=?0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman's rho 0.450, p?=?0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p?=?0.0198) and macrophage (CD68+ cells, rho 0.515, p?=?0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p? less then ?0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.Causes of death, in particular deaths due to infection, have not been widely studied in randomised trials in chronic lymphocytic leukaemia. https://www.selleckchem.com/products/torin-1.html With long-term follow-up (median 13 years) we examined the cause of death in 600/777 patients in the LRF CLL4 trial. Blood samples, taken at randomisation from 499 patients, were available for identifying gene mutations. Infection was a cause of death in 258 patients (43%). Patients dying of infection were more likely than those who died of other causes to have received ?2 lines of treatment (194/258 [75%] versus 231/342 [68%], P?=?0.04) and to have died in the winter months (149/258 [58%] versus 166/342 [49%], P?=?0.03), respectively. In patients with mutation data, the factors significantly associated with death from infection versus all other deaths were 11q deletion (47/162 [29%] versus 40/209 [19%], P?=?0.03) and mutations of the BRAF, FBXW7, NRAS and XPO1 genes. Death was caused by an infection in 46/67 assessable patients (69%) who had a mutation of one or more of these four genes versus only 129/333 patients (39%) without any of these mutations (odds ratio 3.46 [95% CI 1.98-6.07] P? less then ?0.0001). Careful management of infection risk, including prophylaxis against infection, may be important in patients who carry these mutations.Sarcopenia, the age-related loss of skeletal muscle mass and function, affects 5-13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.Native to eastern Asia, the Formosan subterranean termite Coptotermes formosanus (Shiraki) is recognized as one of the 100 worst invasive pests in the world, with established populations in Japan, Hawaii and the southeastern United States. Despite its importance, the native source(s) of C. formosanus introductions and their invasive pathway out of Asia remain elusive. Using ~22,000 SNPs, we retraced the invasion history of this species through approximate Bayesian computation and assessed the consequences of the invasion on its genetic patterns and demography. We show a complex invasion history, where an initial introduction to Hawaii resulted from two distinct introduction events from eastern Asia and the Hong Kong region. The admixed Hawaiian population subsequently served as the source, through a bridgehead, for one introduction to the southeastern US. A separate introduction event from southcentral China subsequently occurred in Florida showing admixture with the first introduction. Overall, these findings further reinforce the pivotal role of bridgeheads in shaping species distributions in the Anthropocene and illustrate that the global distribution of C.